Mouse and Human Models for Investigating Influences of Tau on Progression of Alzheimer's Disease Following Traumatic Neuronal Injury

Abstract

We have completed the design, fabrication, and validation of a new biomedical device to impose moderate mechanical loads on cultured stem-cell derived neuronal and glial cells. Using this device, we assessed morphological changes, beta amyloid production, and tauphosphorylation (i.e., multiple Alzheimer's-associated outcomes) following rapid stretch of iPSC-derived neurons. Results suggest that neurites oriented in the direction of substrate stretch were non-elastically deformed, the cytoskeleton was reorganized, a myloid precursor protein transport was perturbed, amyloid production was increased, and tau phosphorylation unchanged following a single bout of mechanical loading. Multiple bouts of mechanical loading amplified amyloid and tau phenotypes, suggesting a dependence of these Alzheimer's associated outcomes to injury dose or severity.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2017
Accession Number
AD1048149

Entities

People

  • Sameer B Shah

Organizations

  • University of California, San Diego

Tags

DTIC Thesaurus Topics

  • Alzheimer Disease
  • Biology
  • Brain Injuries
  • Cells
  • Cellular Structures
  • Cytoskeleton
  • Diseases And Disorders
  • Electronic Mail
  • Literature Surveys
  • Local Governments
  • Medical Personnel
  • Neuroglia
  • Phenotypes
  • Phosphorylation
  • Stem Cells
  • Students

Fields of Study

  • Biology

Readers

  • Mechanical Engineering/Mechanics of Materials.
  • Molecular and Cellular Biology
  • Traumatic Brain Injury (TBI) and Cognitive Aging in the Guam and Border Populations Affected by Alzheimer's Disease and Tau-Associated Dementias.

Technology Areas

  • Biotechnology